Aortic Stiffness and Cardiovascular Risk in Women with Previous Gestational Diabetes Mellitus

Abstract

Gestational diabetes mellitus (GDM) is a significant risk factor for cardiovascular disease (CVD) in later life, but the mechanism remains unclear. The aim of the study was to investigate indices of glucose metabolism, dyslipidemia, and arterial stiffness (as measured by pulse wave velocity (PWV)), in women with and without a history of GDM, using both the old WHO and new IADPSG diagnostic criteria, at 5 years after the index pregnancy. Dyslipidemia and PWV were used as surrogate markers for CVD risk. The population-based prospective cohort included 300 women from the original STORK study. All participants had an oral glucose tolerance test (OGTT) during pregnancy. Five years later, the OGTT was repeated along with dual-energy x-ray absorptiometry, lipid analysis, and PWV analysis. Measurements were compared between those women who did and did not have GDM based on both the WHO and IADPSG criteria. We found that women with GDM based on the old WHO criteria had higher CVD risk at 5 years than those without GDM, with markedly elevated PWV and more severe dyslipidemia (higher triglycerides (TG)/HDL cholesterol ratio). After adjusting for known risk factors, the most important predictors for elevated PWV and TG/HDL-C ratio at 5-year follow-up were maternal age, BMI, GDM, systolic blood pressure, and indices of glucose metabolism in the index pregnancy. In conclusion, we found a higher risk for CVD, based on the surrogate markers PWV and TG/HDL-C ratio, at 5-year follow-up in women diagnosed with GDM in the index pregnancy when using the old WHO diagnostic criteria.

Fig 1. Glucose tolerance in late pregnancy is associated with an elevated PWV and TG/HDL-C ratio at 5-year follow-up.

Receiver operating characteristic (ROC) curves for predicting (A) PWV and (B) TG/HDL-C ratio by HOMA-IR (green line), insulin sensitivity (black line), beta-cell function (red line), fasting glucose (light blue dotted line), glucose 60 min (dark blue dotted line) glucose 120 min (brown dotted line) in pregnancy. *Risk is expressed as 1-AUC for beta-cell function and insulin sensitivity for comparison reasons.

Fig 2. Relationship between measurements of glycemic control and vascular stiffness at 5-year follow-up in patients with (red circles) and without GDM (green circles) in the index pregnancy.

(A) Associations between PWV, TG/HDL-C ratio and glucose levels during OGTT, HOMA-IR, insulin sensitivity and beta-cell function in the whole cohort at follow-up. (B) Interaction analysis between GDM (red) and indices of glucose metabolism on the TG/HDL ratio. (C) Interaction analysis between BMI and SBP and indices of glucose metabolism on the TG/HDL ratio.